This website is intended for healthcare professionals only.
Take a look at a selection of our recent media coverage:
27th June 2024
The use of biosimilars in Crohn’s disease is steadily increasing due to their cost-effectiveness, efficacy and favourable safety profiles, as demonstrated in recent studies such as iBaSS. Here, Dr João Gonçalves PhD – one of this study’s authors – discusses the team’s findings and the impact he anticipates this new understanding of biosimilar adalimumab having on clinical practice and healthcare policy.
Crohn’s disease is a chronic inflammatory bowel disease (IBD) characterised by relapsing inflammation of the gastrointestinal tract, leading to progressive damage. Patients with Crohn’s disease experience symptoms such as abdominal pain, diarrhoea and fatigue, and can develop long-term complications such as strictures and fistulas.
Biological therapies, particularly those targeting tumour necrosis factor-alpha (TNFα), such as adalimumab, have significantly improved patient outcomes by reducing complications, surgeries and hospitalisations. However, the high cost of these biologics places a substantial financial burden on healthcare systems and patients alike.
Biosimilars are biologic drugs that are highly similar to already approved ‘reference’ biologics and offer a promising solution to reduce healthcare costs. Since biosimilar adalimumab became available in Europe in 2018, it has provided a more cost-effective alternative while maintaining the efficacy and safety profile of the reference product.
A recent study by Young et al investigated the clinical outcomes and patient experiences of transitioning from reference adalimumab (brand name Humira) to a biosimilar adalimumab (SB5; brand name Imraldi) and looked to address concerns about multiple product transitions and their impact on patient care and satisfaction.1
iBaSS, a phase IV prospective, randomised, single-blind, crossover study involving adult Crohn’s disease patients at the University Hospital Southampton NHS Foundation Trust, aimed to mimic the real-world transition process between biosimilar and reference adalimumab.1
Eligible patients were those in remission or with mild disease activity who were established on a stable dose of reference adalimumab or SB5. Critical exclusion criteria included planned discontinuation of adalimumab, scheduled surgeries or hospitalisation within 12 months of randomisation, and pregnancy or breastfeeding.
Participants were randomised to two treatment sequences: one group received reference adalimumab followed by SB5, and the other received SB5 followed by reference adalimumab.
The primary endpoint was the proportion of patients maintaining baseline clinical status throughout each treatment period. Secondary endpoints included changes in disease activity, medical treatment, immunogenicity, biochemical markers and safety.
Of 318 pre-screened patients, 112 participants were enrolled, with 94 (83.9%) completing the 48-week trial. The primary endpoint was achieved by 81.8% of participants treated with reference adalimumab and 79.5% treated with SB5, indicating similar efficacy between the two products.
Scores for disease activity, measured by the modified Harvey-Bradshaw Index (mHBI) and biochemical markers, were consistent across both treatment phases.
Patient-reported outcomes, assessed using the IBD-Control questionnaire and Treatment Satisfaction Questionnaire for Medication (TSQM), showed no significant difference in disease control and overall satisfaction between the two products.
However, SB5 was associated with higher injection pain scores, likely due to its citrate-based formulation compared with the citrate-free reference adalimumab.
Adalimumab serum trough levels and anti-adalimumab antibody concentrations remained stable throughout both treatment phases, suggesting no increased immunogenicity with multiple product transitions.
The safety profile of SB5 was comparable to that of reference adalimumab, with similar rates of adverse events and serious adverse events reported in both groups.
This study highlights the clinical equivalence of SB5 to reference adalimumab in treating Crohn’s disease, supporting the use of biosimilars as a cost-effective alternative without compromising patient outcomes.
The findings are significant in healthcare systems aiming to manage the high costs associated with biologic therapies. The availability of biosimilars can potentially increase patient access to effective treatments and reduce financial strain on healthcare budgets.
One of the strengths of this study is its real-world applicability as it closely mimics the transition process between biosimilar and reference products. The crossover design allowed each participant to experience both treatments, providing direct comparative data on patient satisfaction and efficacy.
Moreover, using patient-reported outcomes, such as the IBD-Control questionnaire and TSQM, offers valuable insights into patient perspectives on disease control and treatment satisfaction.
The higher injection pain scores associated with SB5 highlight the importance of considering patient comfort and experience when selecting biosimilar products. Although this difference was generally manageable, it underscores the need for healthcare providers to address potential concerns and support patients through the transition process.
Effective communication and patient education can help mitigate the ‘nocebo’ effect, where negative expectations about a new treatment might lead to perceived or actual adverse effects.
Despite its strengths, the study faced limitations, including underpowering due to recruitment challenges exacerbated by the Covid-19 pandemic. The pandemic disrupted clinical research activities, reducing the number of participants and potentially affecting the generalisability of the findings.
Additionally, the single-blind design, where participants were aware of the treatment they received, could introduce bias, although efforts were made to minimise this through educating and monitoring patients.
The findings from this study have several implications for clinical practice and healthcare policy.
First, SB5’s demonstrated equivalence to reference adalimumab supports the broader adoption of biosimilars in clinical practice, potentially leading to significant cost savings for healthcare systems. These savings can be redirected to other areas of patient care, improving overall healthcare delivery.
The study underscores the importance of patient-centred care for healthcare providers in managing transitions between biologics. Ensuring patients are well-informed and supported during the transition can enhance adherence and treatment satisfaction, ultimately leading to better clinical outcomes.
Providers should also be aware of the potential for higher injection pain with specific biosimilar formulations and consider this when discussing treatment options with patients.
From a policy perspective, the study highlighted the need for continued investment in biosimilar development and market competition.
As more biosimilars become available, increased competition can drive costs down further, making biologics more accessible to a broader patient population. Policymakers should also consider implementing strategies to support patients during transitions, such as educational programmes and resources for healthcare providers.
While this study provides valuable evidence supporting the use of biosimilar adalimumab in Crohn’s disease treatment, further research is needed to address remaining questions and explore new areas of interest.
Future studies could focus on long-term outcomes of biosimilar use, including the impact of multiple product switches on immunogenicity and clinical efficacy over extended periods.2,3
Additionally, research exploring the nocebo effect in greater detail could provide insights into managing patient expectations and improving treatment experiences.
Qualitative studies, such as patient interviews and focus groups, can offer a deeper understanding of patient perspectives and identify factors influencing treatment satisfaction and adherence.
Another important area for future research is investigating the cost-effectiveness of biosimilars in different healthcare settings and patient populations. Economic evaluations can help quantify the potential savings and benefits of adopting biosimilars, informing healthcare policy decisions and resource allocation.
This study has demonstrated the clinical equivalence and safety of biosimilar adalimumab compared to reference adalimumab in treating Crohn’s disease. The findings support the broader use of biosimilars as a cost-effective alternative to reference biologics, with potential benefits for healthcare systems and patients.
While the higher injection pain associated with biosimilar adalimumab warrants consideration, effective patient education and support can help mitigate concerns and enhance treatment satisfaction.
Overall, the research provides a strong foundation for the continued adoption of biosimilars in clinical practice, contributing to more sustainable healthcare models and improved access to biologic therapies.4–6
Further studies are needed to expand on these findings and address remaining challenges, ensuring that patients receive the best possible care in the evolving landscape of biologics.
João Gonçalves PharmD PhD
Faculty of Pharmacy, University of Lisbon, Portugal
1st March 2024
Top-down treatment with infliximab plus an immunomodulator substantially improves outcomes for patients with newly diagnosed Crohn’s disease compared with accelerated step-up therapy, UK research finds.
Previous trials had supported earlier use of anti-tumour necrosis factor therapy, usually in combination with an immunomodulator, researchers wrote in The Lancet Gastroenterology and Hepatology.
However, the most common strategy in the UK and globally was an accelerated step-up approach, where treatment is escalated until the tendency to relapse is controlled, they said.
The multi-centre PROFILE trial enrolled 386 patients aged 16-80 years with newly diagnosed, active Crohn’s disease, who had raised C-reactive protein, calprotectin of 200 μg/g or more, plus active inflammation on ileo-colonoscopy.
Patients were stratified based on a blood-based biomarker previously found to correlate with the need for future treatment escalation and then randomised to either top-down therapy or the accelerated step-up approach.
Over 48 weeks off follow-up, the biomarker did not show any clinical utility.
However, 79% of patients achieved sustained steroid-free and surgery-free remission in the top-down group, compared with 15% in the conventional therapy group, a 64-percentage point difference, they reported.
‘Top-down treatment also showed greater efficacy in achieving endoscopic remission, improved quality of life, and reduced number of flares requiring treatment escalation,’ they wrote.
It was also safer than conventional therapy for Crohn’s disease, with fewer adverse and serious adverse events and no increased rate of infection.
A reduced need for urgent abdominal surgery was also found, with one person in the top-down group requiring surgery for complications, compared with 10 people in the step-up group, they added.
‘These findings are potentially transformative for the management of Crohn’s disease,’ the study authors concluded.
‘While PROFILE did not identify a clinically useful biomarker, it has provided clear evidence with regards to optimal treatment strategy from diagnosis.’
First author Dr Nuru Noor, of the Department of Medicine at the University of Cambridge, said the study findings redefined what should be considered as early treatment for Crohn’s disease.
‘Historically, treatment with an advanced therapy like infliximab within two years of diagnosis has been considered ‘early’ and an ‘accelerated step-up’ approach therefore “good enough”,’ he said.
‘As soon as a patient is diagnosed with Crohn’s disease, the clock is ticking – and has likely been ticking for some time – in terms of damage happening to the bowel, so there’s a need to start on an advanced therapy such as infliximab as soon as possible.’
Chief investigator Professor Miles Parkes, who is director of the NIHR Cambridge Biomedical Research Centre, said the study showed clinicians could prevent most adverse outcomes for Crohn’s disease, including need for urgent surgery, with a treatment strategy that was safe and becoming increasingly affordable.
‘If you take a holistic view of safety, including the need for hospitalisations and urgent surgery, then the safest thing from a patient point of view is to offer “top-down” therapy straight after diagnosis rather than having to wait and use “step-up” treatment,’ he said.
In February 2023, the Medicines and Healthcare products Regulatory Agency approved upadacitinib for use in patients with moderate to severely active Crohn’s disease who have had either an inadequate response, or were intolerant to, conventional therapy or a biological agent.
27th September 2023
The use of risankizumab (brand name Skyrizi) in the treatment of adult patients with moderately to severely active Crohn‘s disease met the two primary endpoints in a head-to-head study compared to ustekinumab, its manufacturer AbbVie has announced.
While both risankizumab and ustekinumab are already approved for Crohn‘s disease and other conditions, their modes of action are different, with the former selectively blocking interleukin-23 (IL-23) signalling and the latter blocking both IL-12 and IL-23. The researchers therefore sought to determine if these differences affect treatment outcomes.
In the phase 3, multi-centre, randomised, head-to-head SEQUENCE study, the primary endpoint was non-inferiority for clinical remission at week 24 and superiority of endoscopic remission at week 48.
All participants had a confirmed diagnosis of Crohn‘s disease for at least three months and a Crohn‘s Disease Activity Index (CDAI) score of 220 to 450 at baseline. They were also considered to have moderate-to-severe disease based on an assessment of stool frequency, abdominal pain score, their Simple Endoscopy Score for Crohn‘s Disease (SES-CD), and a demonstrated intolerance or inadequate response to one or more anti-TNF therapies.
Participants assigned to risankizumab received a 600 mg intravenous induction at Weeks 0, 4 and 8 and 360 mg subcutaneous injection starting at week 12 and every eight weeks thereafter, through to week 48.
The results of the first primary endpoint, clinical remission (per CDAI, defined as CDAI <150) at week 24, met non-inferiority of risankizumab versus ustekinumab (non-inferiority margin of 10%). Remission rates were 59% in the risankizumab group and 40% in the ustekinumab group.
For the second primary endpoint of endoscopic remission (SES-CD ≤4 and at least a two-point reduction versus baseline and no sub-score greater than 1 in any individual component) at week 48, risankizumab provided a remission rate of 32% compared to 16% in the ustekinumab group (p < 0.0001).
In a commentary of these results, Dr Laurent Peyrin-Biroulet, director of the Infinity Institute, professor of gastroenterology and head of the inflammatory bowel disease group at the gastroenterology department, University Hospital of Nancy in France, said: ‘These results add to our growing body of evidence for Skyrizi in Crohn‘s disease. This study highlights the efficacy of Skyrizi compared to ustekinumab in helping eligible patients achieve clinical and endoscopic treatment goals and also reinforces the safety profile observed in previous studies.’
Full results from the SEQUENCE study will be presented at a future medical meeting and submitted for publication in a peer-reviewed journal.
13th February 2023
Upadacitinib (brand name Rinvoq) was previously been approved for ulcerative colitis and is now licensed in moderate to severe Crohn’s disease.
The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has now approved upadacitinib for use in patients with moderate to severely active Crohn’s disease and who have had either an inadequate response or were intolerant to, conventional therapy or a biological agent.
Crohn’s disease is a form of inflammatory bowel disease that affects any part of the gastrointestinal tract and which is thought to affect around 10 million people worldwide and has a major impact on health-related quality of life.
Patients with Crohn’s will often receive oral corticosteroids to manage a disease flare, although those with more severe disease receive biologics either with or without immunomodulators to induce and maintain remission.
Upadacitinib is a Janus kinase inhibitor and a Phase II trial, evaluating the efficacy of 3 mg, 6 mg, 12 mg 24 mg twice daily or 24 mg daily, concluded that the drug induced endoscopic remission in a significant proportion of patients in comparison to placebo.
The MHRA decision was based on the findings of three other clinical studies and are reported in the press release.
In the first, U-EXCEED, a significantly higher proportion of patients treated with upadacitinib 45 mg daily achieved clinical remission per SF/AP at week 12 compared to placebo (40% vs 14%, p<0.001) and an endoscopic response compared to placebo (35% vs 4%, p<0.001).
In the second trial, U-EXCEL, again more patients given a 12-week induction regimen of upadacitinib 45 mg daily achieved clinical remission (51% vs 22%, p < 0.001) and endoscopic response (46% vs 13%, p < 0.001) compared to placebo.
In the third study, U-ENDURE which was a maintenance trial, patients who had responded to 12 weeks of upadacitinib 45 mg, were re-randomised to 15 mg, 30 mg or placebo and assessed at week 52.
The results showed that clinical remission occurred in 36 and 46% respectively (i.e., for 15 and 30 mg) compared to 14% for placebo (p < 0.001).
Similarly, endoscopic response occurred in 28 and 40% compared to 7% in the placebo group (p < 0.001).
Interestingly, a recently published real-world study of upadacitinib in patients with Crohn’s disease has shown that the drug induced subjective and objective responses in 25% and 42% of patients, respectively.
Updated information on the indications for rinvoq can be found in the summary of product characteristics.
Download Hospital Healthcare Europe free app
© Cogora 2024
Cogora Limited. 1 Giltspur Street, London EC1A 9DD
Registered in the United Kingdom. Reg. No. 2147432
